Larimar Therapeutics, Inc. · NASDAQ:LRMR
Larimar Therapeutics — Investor Presentation (August 2022)
34 slides from Larimar Therapeutics's investor presentation, Aug 11, 2022
Slide 1: Larimar Therapeutics Corporate Presentation
August 2022 Larimar Therapeutics Corporate Presentation Exhibit 99.2
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains forward-looking statements that are based on the beliefs and assumptions of Larimar Therapeutics, Inc. (the “Company”) and on information currently available to management. All statements contained in this presentation other than statements of hi
Slide 3: Investment Highlights
Investment Highlights Double-blind, placebo-controlled Phase 1 proof-of-concept trials in FA patients complete Data show dose dependent increases in frataxin (FXN) levels from baseline compared to placebo in all evaluated tissues with daily dosing & that CTI-1601 was generally well tolerated when do
Slide 4: Platform Technology is Supported by a Strong IP Portfolio
2005 2010 2020 2025 2030 2035 2040 2045 2000 2015 TAT-MTS-FXN Composition of Matter (broad coverage of CTI-1601) US 9,045,552 (Exclusive license from Wake Forest) Expiration October 2024 Methods of treating FA using TAT-MTS-FXN and delivering TAT-MTS-FXN to mitochondria (broad coverage of CTI-1601)
Slide 5: Friedreich's Ataxia disease overview
Caused by genetic defect resulting in low levels of frataxin Patients with FA only produce ~20-40% of normal frataxin levels depending on the tissue, sampling technique, and assay considered1 Affects ~20,000 patients globally, with ~5,000 patients in the U.S. and majority of the remaining patients i
Slide 6: CTI-1601 is Designed to Deliver Additional Frataxin
CTI-1601 is Designed to Deliver Additional Frataxin (FXN) The maintenance of the cleavage site allows the CPP and MTS to be removed by mitochondrial processing peptidase to produce mature human FXN in the mitochondria STRUCTURE OF ENDOGENOUS FXN STRUCTURE OF CTI-1601 Cleavage by mitochondrial proces
Slide 7: Phase 1 Topline Data Demonstrated POC for CTI-1601 in FA
CTI-1601 appears to be generally well tolerated at doses up to 100 mg administered daily for 13 days Phase 1 Topline Data Demonstrated POC for CTI-1601 in FA Daily dosing of CTI-1601 resulted in dose-dependent increases in FXN levels from baseline compared to placebo controls in all evaluated tissue
Slide 8: CTI-1601: Phase 1 Clinical Program in Patients with FA
CTI-1601: Phase 1 Clinical Program in Patients with FA Phase 1 Development Plan Two double-blind, placebo-controlled dosing trials in patients with FA Patient dosing began December 2019 Safety Review Committee assessed all blinded data between each cohort to ensure patient safety Number of subjects:
Slide 9: MAD Trial Patient Enrollment
MAD Trial Patient Enrollment MAD Trial Patient Enrollment (n=27) Parameter Statistic Overall Participated in SAD trial? Yes n (%) 16 (59%) No n (%) 11 (41%) Cohort 1 (25 mg) Active vs. Placebo Active n (%) 6 (75%) Placebo n (%) 2 (25%) Cohort 2 (50 mg) Active vs. Placebo Active n (%) 7 (78%) Placebo
Slide 10: Multiple Ascending Dose Study Design
Multiple Ascending Dose Study Design Treatment Schedules for Each Cohort 13-day Treatment Period Cohort 2 (50 mg; n = 9) 2 3 4 5 1 6 7 8 9 10 11 12 13 14 = Administration of CTI-1601 or placebo = No Administration 13-day Treatment Period Cohort 1 (25 mg; n = 8) 2 3 4 5 1 6 7 8 9 10 11 12 13 14 = Adm
Slide 11: Data Compare Favorably to FXN Levels Expected in Heterozygous Carriers
Data Compare Favorably to FXN Levels Expected in Heterozygous Carriers Achieved median FXN levels that were >60% of the median FXN levels observed in healthy controls FXN* Levels By Dose Group (Buccal Cells) FXN Level (pg/μg total protein) Baseline Day 4/7 Day 13 *FXN levels measured via detection o
Slide 12: Dose Dependent Increases in FXN Levels Observed in Buccal Cells
Dose Dependent Increases in FXN Levels Observed in Buccal Cells Daily SC injections of 100 mg CTI-1601 resulted in an ~2.5 fold increase in FXN levels from baseline FXN* Levels By Dose Group (Buccal Cells) FXN* Change from Baseline By Dose Group (Buccal Cells) Additional FXN (Change from Baseline) (
Slide 13: Dose Dependent Increases in FXN Levels Observed in Skin
Dose Dependent Increases in FXN Levels Observed in Skin Daily SC injections of 100 mg CTI-1601 resulted in an ~3 fold increase in FXN levels from baseline FXN* Levels By Dose Group (Skin Biopsies) FXN* Change from Baseline By Dose Group (Skin Biopsies) Day 13 Baseline Day 13 *FXN levels measured via
Slide 14: Dose Dependent Increases in FXN Levels Observed in Platelets
Dose Dependent Increases in FXN Levels Observed in Platelets with Daily Dosing Daily SC injections of 100mg CTI-1601 resulted in increases in FXN levels from baseline compared to placebo FXN* Levels By Dose Group (Platelets) FXN* Change from Baseline By Dose Group (Platelets) Day 4/7 Day 13 Baseline
Slide 15: Summary of MAD trial safety data
Summary of MAD trial safety data: Repeated doses (25 mg, 50 mg, and 100 mg) of CTI-1601 or placebo were administered subcutaneously. 27 patients were dosed in the trial. 26 patients completed the trial. 1 patient receiving CTI-1601 in Cohort 2 (50 mg) withdrew after experiencing mild/moderate sympto
Slide 16: Summary of PK Analyses
Summary of PK Analyses CTI-1601 was quickly absorbed after subcutaneous administration Dose-proportional increases in exposure observed with increasing doses of CTI-1601 Mean half life of CTI-1601 in plasma was approximately 11 hours CTI-1601 appears to be at or close to steady state exposure after
Slide 17: Phase 1 Topline Data Demonstrated POC for CTI-1601 in FA
Phase 1 Topline Data Demonstrated POC for CTI-1601 in FA FXN levels in buccal cells & blood have been shown to correlate with disease severity in FA patients1 Dosing Frataxin Measurements Daily SC injections of CTI-1601 resulted in dose-dependent increases in FXN levels from baseline compared to pla
Slide 18: Upcoming CTI-1601 Trials and Regulatory Interactions
Upcoming CTI-1601 Trials and Regulatory Interactions Future Planned Trials and Regulatory Interactions Include: Additional analyses from the Phase 1 program planned for presentation at scientific meetings Global double-blind placebo-controlled pivotal trial Continued FDA interactions around the clin
Slide 19: Investment Highlights
Investment Highlights Double-blind, placebo-controlled Phase 1 proof-of-concept trials in FA patients complete Data show dose dependent increases in frataxin (FXN) levels from baseline compared to placebo in all evaluated tissues with daily dosing & that CTI-1601 was generally well tolerated when do
Slide 20: Thank You
THANK YOU Larimar Therapeutics Corporate Presentation
Slide 21: Leadership Team
Leadership Team Nancy Ruiz, MD, FACP, FIDSA Chief Medical Officer John Berman, CPA VP, Finance & Operations David Bettoun, PhD VP, Discovery & Non-clinical R&D Noreen Scherer VP, Clinical Operations Michael Celano Chief Financial Officer Keith E. Lynch, Jr. VP, Manufacturing and Supply Chain Francis
Slide 22: Recent and Upcoming Scientific Presentations
Recent and Upcoming Scientific Presentations Conference Dates Conference Name Summary of Presentation(s) Recent Presentations May 26 – 28, 2022 4th Pan American Parkinson’s Disease and Movement Disorders Congress Two abstracts accepted. Included safety, pharmacokinetic, and pharmacodynamic data from
Slide 23: Strong Relationship with FARA
Company has strong relationship with Friedreich’s Ataxia Research Alliance (FARA) National, non-profit organization dedicated to the pursuit of scientific research leading to treatments and a cure for FA FARA provides industry with several key items Assistance with patient recruitment and education
Slide 24: Scientific Advisory Board
Scientific Advisory Board Giovanni Manfredi, MD, PhD Finbar and Marianne Kenny Professor in Clinical and Research Neurology at Weill Cornell Medicine. Professor of Neuroscience at Weill Cornell Medicine. Russell Clayton, DO (Chairman) Former Chief Medical Officer at Alcresta Therapeutics, a medical
Slide 25: MAD Trial Patient Demographics
MAD Trial Patient Demographics Parameter Statistic All placebo (n=7) 25 mg CTI-1601 (n=6) 50 mg CTI-1601 (n=7) 100 mg CTI-1601 (n=7) All CTI-1601 (n=20) Overall (n=27) Sex Male n (%) 5 (71.4) 3 ( 50.0) 4 ( 57.1) 3 ( 42.9) 10 ( 50.0) 15 (55.6) Female n (%) 2 (28.6) 3 ( 50.0) 3 ( 42.9) 4 ( 57.1) 10 (
Slide 26: MAD Trial Patient Disease Characteristics
MAD Trial Patient Disease Characteristics Parameter Statistic All placebo (n=7) 25 mg CTI-1601 (n=6) 50 mg CTI-1601 (n=7) 100 mg CTI-1601 (n=7) All CTI-1601 (n=20) Overall (n=27) Age at Symptom Onset Mean 14.1 24.0 19.3 11.9 18.1 17.1 SD 5.34 14.48 6.21 6.72 10.37 9.39 Median 15.0 18.0 19.0 10.0 18.
Slide 27: CTI-1601: Positive Mouse Model Data Support Development
CTI-1601: Positive Mouse Model Data Support Development Cardiac Knock Out Mouse Model Studies (MCK-Cre FXN KO Mouse) Proof-of-Concept Demonstrated In Mouse Models of FA Neurologic Knock Out Mouse Model Study (Pvalb-CRE FXN KO Mouse) Extended survival Prevented development of ataxic gait Demonstrated
Slide 28: CTI-1601 Extends Survival in FXN-deficient KO Mice
CTI-1601 Extends Survival in FXN-deficient KO Mice Median Survival of MCK-Cre FXN-KO Mice 166 days (CTI-1601) vs. 98 days (Vehicle) CTI-1601 was administered 10 mg/kg SC every other day Survival beyond vehicle mean (107.5 days) 87.5% (CTI-1601) vs. 33% (Vehicle) Demonstrates that CTI-1601 is capable
Slide 29: In-Vivo Efficacy Data in Neurologic KO Mouse Model
Pvalb-Cre FXN-KO mouse Single dose level: 10 mg/kg CTI-1601 or vehicle given intraperitoneally three times per week hFXN replacement with CTI-1601 prevents the development of ataxic gait CTI-1601-treated mice survive longer than untreated mice Human frataxin present in brain, dorsal root ganglia and
Slide 30: CTI-1601 Delivers hFXN to Mitochondria in KO Mice
CTI-1601 Delivers hFXN to Mitochondria in KO Mice hFXN concentration within mitochondria increases in a dose-dependent manner Given subcutaneously, CTI-1601 functionally replaces hFXN in mitochondria of KO mice Succinate dehydrogenase (SDH) activity, which is indicative of mitochondrial function, in
Slide 31: CTI-1601 Prevents Left Ventricle Dilation in KO Mice
CTI-1601 Prevents Left Ventricle Dilation in KO Mice Left ventricular (LV) volume increases in systole in untreated mice by 8 weeks (after 4 weeks of dosing with vehicle), but remains similar to wildtype when treated with CTI-1601 (10 mg/kg every other day) CTI-1601-treated mice have similar LV volu
Slide 32: CTI-1601 Preserves Left Ventricle Function in KO Mice
CTI-1601 Preserves Left Ventricle Function in KO Mice Left ventricular (LV) function drops significantly in vehicle treated mice by week 8 CTI-1601-treated (10 mg/kg every other day) mice have similar LV as healthy controls; echocardiogram shows significant differences between vehicle and CTI-1601 t
Slide 33: Favorable PK/PD Profile in Healthy Cynomolgus Monkeys
Favorable PK/PD Profile in Healthy Cynomolgus Monkeys CTI-1601 is bioavailable when given subcutaneously Sustained levels of hFXN are found in blood cells (platelets) and peripheral tissues (buccal cells, skin) as early as the 7th day and still present after 14 days Sustained levels of hFXN are foun
Slide 34: Biodistribution in Healthy Cynomolgus Monkeys
Biodistribution in Healthy Cynomolgus Monkeys Treatment of monkeys with CTI-1601 results in sustained levels of hFXN in peripheral tissues that are accessible in the clinic FXN levels increase ~4X or more following CTI-1601 administration For comparison, FA patients show FXN levels that range from ~
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